Zonulin: A Protein with Implications for Gut Health and Disease
Zonulin, also known as haptoglobin 2 precursor,[1] is a protein that plays a crucial role in regulating the permeability of tight junctions between cells lining the digestive tract. These tight junctions act as a selective barrier, allowing the passage of essential nutrients while restricting the passage of harmful substances. Zonulin's ability to modulate the opening and closing of these tight junctions has significant implications for gut health and disease.
In 2000, Alessio Fasano and his team at the University of Maryland School of Medicine discovered zonulin. They observed striking similarities between zonulin and zonula occludens toxin, a bacterial toxin produced by the cholera pathogen Vibrio cholerae. This toxin is responsible for the watery diarrhea characteristic of cholera, and its mechanism of action involves opening tight junctions in the intestinal lining.
Zonulin's role in intestinal permeability has been implicated in the development of various diseases, including celiac disease, type 1 diabetes, and type 2 diabetes. In celiac disease, zonulin production is triggered by gliadin, a protein found in gluten. This increased zonulin production contributes to intestinal permeability, allowing gluten fragments to pass through the intestinal wall and trigger an autoimmune response.
Similarly, in type 1 diabetes, zonulin production is associated with an increased risk of developing the disease. Zonulin may play a role in the disruption of the intestinal barrier, allowing antigens to enter the bloodstream and trigger an autoimmune attack against insulin-producing cells in the pancreas.
Type 2 diabetes is also linked to elevated zonulin levels. Increased zonulin production may contribute to metabolic endotoxemia, a condition characterized by the presence of bacterial toxins in the bloodstream. Metabolic endotoxemia is associated with various complications of type 2 diabetes, including insulin resistance and inflammation.
Given its role in regulating intestinal permeability, zonulin has emerged as a potential therapeutic target for various diseases. Zonula occludens toxin, the bacterial counterpart to zonulin, is being investigated as an adjuvant to improve the absorption of drugs and vaccines. Additionally, zonulin receptor antagonists, such as larazotide acetate, are being explored for their potential to treat celiac disease and other conditions associated with increased intestinal permeability.
In conclusion, zonulin is a protein with multifaceted effects on intestinal permeability and is implicated in the development of various diseases. Further research is needed to fully understand the mechanisms by which zonulin regulates intestinal permeability and to develop effective therapeutic strategies targeting zonulin signaling.
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References
- ↑ Fasano, Alessio; Not, Tarcisio; Wang, Wenle; Uzzau, Sergio; Berti, Irene; Tommasini, Alberto; Goldblum, Simeon E (April 2000). "Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease". The Lancet. 355 (9214): 1518–1519. doi:10.1016/s0140-6736(00)02169-3. ISSN 0140-6736.